Pulmonary pharmacology最新文献

Both human and animal studies show that irritation of airway mucosa elicits a variety of reflex responses such as coughing, apnoea, and laryngeal closure. Most of the information concerning these reflex responses were obtained in anesthetized conditions with little applicability to awake conditions. Various aspects of cough and other reflexes on irritation of the airway mucosa are discussed. Studies on awake humans showed that stimulation of the laryngeal mucosa with a small amount of distilled water during wakefulness causes elicitation of the expiration reflex, cough reflex, and swallowing reflex while other types of responses are scarcely observed. In addition, the duration of these responses is remarkably short. In contrast, the same stimulation causes more variant, prolonged, and exaggerated responses during a light depth of anesthesia. An increase in depth of anesthesia abolishes expiratory efforts such as coughing and the expiration reflex whereas the apnoeic reflex and laryngeal closure reflex are resistant to the depressant effect of anesthesia. Also, the respiratory reflex responses to airway irritation varied, depending on the site of stimulation: both laryngeal and tracheal stimulation cause vigorous respiratory responses whereas bronchial stimulation causes little or no respiratory responses. These results indicate not only that the types and magnitude of reflex responses is greatly modified by the central nervous state but also that the site of stimulation is crucial for determining the pattern of respiratory responses elicited by airway stimulation in humans.

Methodology to evaluate the efficacy of antitussive drugs rely largely on subjective methods and cough counts. There are few studies in cough due to natural disease especially using objective techniques. This paper presents data from a series of randomized, double blind, placebo controlled clinical trials in cough due to both chronic bronchopulmonary disease and acute upper respiratory tract infections. In these studies, cough was quantified using a standardized and validated computerized system for the acquisition and multidimensional analysis of the cough sound. Key objective parameters like cough counts, intensity, latency and total effort expended were studied. Guaiphenesin and bromhexine showed significant expectorant effects in patients with productive cough due to chronic bronchopulmonary disease. Differences were observed in speed of action, and objective and subjective measures, that probably indicate differences in drug action. More recently, three studies evaluated the antitussive drug dextromethorphan in non-productive cough due to uncomplicated upper respiratory tract infections. Reproducible cough suppressant effects were demonstrated after a single 30 mg dose using objective measures of cough counts, latency and total effort. These results establish the sensitivity and robustness of the cough quantitation methodology in the objective evaluation of cough treatments.

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Codeine is generally accepted as a standard or reference antitussive against which new antitussive medications can be compared. However there are very few studies which have investigated the antitussive efficacy of codeine using cough associated with upper respiratory tract infection (URTI) and there is little if any evidence to support the antitussive efficacy of codeine in this model. This paper discusses the mechanism of cough in man and describes some clinical investigations on the effects of codeine on cough associated with URTI. The recent clinical investigations do not provide any evidence to support an antitussive action of codeine in the treatment of cough associated with URTI yet there is evidence in the literature which indicates that codeine inhibits fictive cough in animal models and also has antitussive activity against both induced and chronic cough models in man. In order to explain these different effects of codeine on the different models of cough, a hypothesis is put forward that there are two cough pathways in man. A voluntary pathway associated with cough related to URTI which is not affected by codeine, and a reflex pathway associated with induced and chronic cough which is inhibited by codeine

The focus of this review is work that supports a model of the medullary neuronal network that is involved in producing the cough motor pattern of inspiratory and expiratory pump muscles. Evidence is presented that supports the following hypotheses: (1) Bulbospinal drive to respiratory motoneurons during cough arises, at least in part, from the same medullary neurons involved in providing drive during eupnoea. (2) Medullary Bötzinger/rostral ventral respiratory group neurons implicated in generating and shaping the eupnoeic pattern of breathing are also involved in producing the central cough motor pattern. The results were not consistent with a “cough centre” separate from the BÖT/VRG. Observed neurons (in cats) included most of all previously identified respiratory modulated “types”. The results showed that there were alterations in discharge patterns of all respiratory neurons during fictive cough. Many “types” responded as predicted by cough model network simulations. Based on neuron behaviours in our studies and inferred synaptic actions among BÖT/VRG neurons, we propose a preliminary model for cough generation by the BÖT/rVRG network.

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Efforts have been directed to evolve a computerized system for acquisition and multi-dimensional analysis of the cough sound. The system consists of a PC – AT486 computer with an ADC board having 12 bit resolution. The audio cough sound is acquired using a sensitive miniature microphone at a sampling rate of 8 kHz in the computer and simultaneously recorded in real time using a digital audio tape recorder which also serves as a back up. Analysis of the cough sound is done in time and frequency domains using the digitized data which provide numerical values for key parameters like cough counts, bouts, their intensity and latency. In addition, the duration of each event and cough patterns provide a unique tool which allows objective evaluation of antitussive and expectorant drugs. Both on-line and off-line checks ensure error-free performance over long periods of time. The entire system has been evaluated for sensitivity, accuracy, precision and reliability. Successful use of this system in clinical studies has established what perhaps is the first integrated approach for the objective evaluation of cough.